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Does anyone know of a list that categorizes acidic and alkaline
drugs? It would be helpful to have such a list instead of looking
each drug up as questions come up.
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The following message was posted to: PharmPK
Foye's Principles of Medicinal Chemistry has a list in the appendix that
includes pKas.
[Also Martin's Physical Pharmacy - db]
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The following message was posted to: PharmPK
Hi everbody,
I have molecules of oxazolidinones series having good invitro
activity but fails in solubility in DMSO and water. Kindly give
latest update of any improvement of Pka of this class of compound and
possibly any software to predict and improve this property of
oxazolidiones in general.
With thanks !
B.Nataraj
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The following message was posted to: PharmPK
Hi Nataraj,
You can use surfactants (such as polysorbate-80, Cremophor-EL etc) or
complexation agents (such as beta-cyclodextrin, Captisol etc) to enhance
solubility.
pKa of a drug compound is determined by the functional groups located on
it. In general, acidic functional groups have low pKa (eg. carboxylic
acids have pKa around 3 to 4) and basic functional groups have high
pKa. (eg. amino compounds have pKa around 7 to 8). As a result, at
physiological pH ( around 7.4), both acidic and basic compounds get
ionised, the extent of which depends on the actual pKa and pH of the
medium. However, overall solubility is dictated by the lipophilic nature
of the compound denoted as Log P (log n-octonol/water partition
coefficient) in case of neutral compounds and Log D (distribution
coefficient) in case of ionisable compounds.
pKa of a chemical compound can be altered by modifying the functional
groups, but that may not always result in enhanced solubility as
solubility not dictated by pKa alone. In cases where the functional
groups are responsible for the pharmacological activity, alteration
would result in the loss of activity. Also, drug compounds have to be
optimally lipophilic in nature in order to cross various lipidic
membranes that come in its path before reaching the site of action.
So, solubility issues can be addressed to some extent by altering the
chemical structure (which is done at the discovery level). But, if that
fails to address, solubility issues can be overcome by employing
suitable formulation techniques (often done at the late stages of drug
development).
Hope this helps.
Kasiram.
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The following message was posted to: PharmPK
Hi Nataraj:
I will look into the first 10 pages of Wilson and Giswold "Text Book of
Organic Medicinal and Pharmaceutical Chemistry" this book catalogued
list of most of the drugs and their physico chemical properties in one
place. Let me know if you can't get copy of it I can mail you one.
Good luck,
Prasad Tata
Saint Louis, MO
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)